Center for Reproductive MedicineRen Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
Shanghai Key Laboratory for Assisted Reproduction and Reproductive GeneticsShanghai, China.
Reproduction. 2017 Oct;154(4):483-496. doi: 10.1530/REP-17-0157. Epub 2017 Jul 20.
Poor ovarian response is a significant problem encountered during fertilization and embryo transfer procedures. Many infertile women may suffer from poor ovarian response and its incidence tends to be increasing in young patients nowadays. It is a major cause of maternal infertility because it is associated with low pregnancy and live birth rates. However, the cause of poor ovarian response is not clear. In this study, we extracted microRNAs from human follicular fluid and performed miRNA sequencing to investigate a potential posttranscriptional mechanism underlying poor ovarian response. The results showed that many miRNAs were obviously different between the poor ovarian response and non-poor ovarian response groups. We then performed quantitative polymerase chain reaction, Western blot analysis and used an culture system to verify the sequencing results and to study the mechanism. Notably, we found that miRNA-15a-5p was significantly elevated in the young poor ovarian response group. Furthermore, we demonstrated that high levels of miR-15a-5p in the young poor ovarian response group repressed granulosa cell proliferation by regulating the PI3K-AKT-mTOR signaling pathway and promoted apoptosis through BCL2 and BAD. This could explain the reduced oocyte retrieval number seen in poor ovarian response patients.
卵巢反应不良是体外受精和胚胎移植过程中遇到的一个重大问题。许多不孕妇女可能患有卵巢反应不良，而且目前年轻患者的发病率呈上升趋势。它是导致母性不孕的一个主要原因，因为它与低妊娠率和活产率有关。然而，卵巢反应不良的原因尚不清楚。在这项研究中，我们从人卵泡液中提取 microRNAs 并进行 miRNA 测序，以研究卵巢反应不良潜在的转录后机制。结果表明，在卵巢反应不良组和非卵巢反应不良组之间，许多 miRNA 明显不同。然后我们进行了定量聚合酶链反应、Western blot 分析，并使用培养系统来验证测序结果和研究机制。值得注意的是，我们发现 miRNA-15a-5p 在年轻的卵巢反应不良组中明显升高。此外，我们证明年轻的卵巢反应不良组中高表达的 miR-15a-5p 通过调节 PI3K-AKT-mTOR 信号通路抑制颗粒细胞增殖，并通过 BCL2 和 BAD 促进细胞凋亡。这可以解释卵巢反应不良患者取卵数量减少的现象。
